Paweł Plakwicz

Gingival Fibromatosis with Significant De Novo Formation of Fibrotic Tissue and a High Rate of Recurrence.

Patient: Female, 11 Final Diagnosis: Hereditary gingival fibromatosis Symptoms: Gingival overgrowth Medication: — Clinical Procedure: Surgery Specialty: Dentistry Objective: Rare disease Background: Hereditary gingival fibromatosis is characterized by slowly progressive enlargement of the gingiva that can present as an isolated condition or a part of various syndromes. Case Report: An 11-year-old female reported with a gingival lesion that caused masticatory problems and poor oral hygiene. Periodontal examination revealed a dense tissue covering 30% of her teeth crowns within both jaws. Panoramic x-ray showed a normal bone height and teeth positioning. The patient did not use any medications, but a similar condition was also present in other family members. The patient was diagnosed with hereditary gingival fibromatosis. Surgery was carried out to remove excess of gingival tissue. Post-surgical healing was uneventful, but four weeks after the first surgery, the condition recurred amounting to 45% of the initial tissue volume presenting in the mandible, and 25% in the maxilla. Two months later, no significant growth was noted in the mandible, while in the maxilla, growth increased to 40% of the pre-operative state. Analysis by polarized microscope showed a significant increase of thin fibrotic fibrils that contributed 80% of the total pool of collagen fibrils in the patient’s gingiva, but only 25% in healthy gingiva. The patient was receiving outpatient care for follow-up every three months and surgical intervention had not been planned as long as her periodontal health would not be compromised. Conclusions: It is currently not clear whether the extent of the fibrosis had a mechanistic association with the ratio of gingival tissue re-growth in our case study. Further studies are needed to explain this association and improve the management of this condition.

Analysis of mutations in the SOS-1 gene in two Polish families with hereditary gingival fibromatosis

OBJECTIVES To establish whether two families from Malopolska and Mazovia provinces in Poland are affected by hereditary gingival fibromatosis type 1, caused by a single-cytosine insertion in exon 21 of the Son-of-Sevenless-1 gene. MATERIAL AND METHODS Six subjects with hereditary gingival fibromatosis and five healthy subjects were enrolled in the study. Gingival biopsies were collected during gingivectomy or tooth extraction and used for histopathological evaluation. Total RNA and genomic DNA were purified from cultured gingival fibroblasts followed by cDNA and genomic DNA sequencing and analysis. RESULTS Hereditary gingival fibromatosis was confirmed by periodontal examination, X-ray, and laboratory tests. Histopathological evaluation showed hyperplastic epithelium, numerous collagen bundles, and abundant-to-moderate fibroblasts in subepithelial and connective tissue. Sequencing of exons 19-22 of the Son-of-Sevenless-1 gene did not reveal a single-cytosine insertion nor other mutations. CONCLUSIONS Patients from two Polish families under study had not been affected by hereditary gingival fibromatosis type 1, caused by a single-cytosine insertion in exon 21 of the Son-of-Sevenless-1 gene. Further studies of the remaining regions of this gene as well as of other genes are needed to identify disease-related mutations in these patients. This will help to unravel the pathogenic mechanism of gingival overgrowth.

Vertical bone growth following autotransplantation of the developing maxillary third molar to replace a retained mandibular permanent molar: a case report.

A retained permanent mandibular first molar caused arrested development and a defect of the alveolar bone in a 16-year-old girl. Extraction of the ankylosed tooth was immediately followed by autotransplantation of the developing maxillary third molar. At the 3-year follow-up examination the interproximal bone level at the autotransplanted molar was equal to that of the neighboring teeth. Cone beam computed tomography showed bone at the labial aspect of the transplant. The eruption of the autotransplanted tooth stimulated vertical alveolar bone development and repaired the bone defect. Additionally, there was closure of the posterior open bite that was initially present at the ankylosed molar site.

TIMP-1 association with collagen type I overproduction in hereditary gingival fibromatosis

OBJECTIVES To investigate the processes associated with the excessive production of collagen I in hereditary gingival fibromatosis (HGF). MATERIALS AND METHODS Three HGF subjects and five controls were enrolled in the study. Histomorphological and immunohistological analyses were performed on gingival tissues. The expression of heat-shock protein 47 (HSP47), collagen I, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) by gingival fibroblasts isolated from HGF and controls was analysed using qRT-PCR, Western blotting and ELISA. RESULTS Considerable accumulation of fibrotic fibrils and increased synthesis of HSP47 were noted in HGF gingival tissues. The synthesis of collagen I, HSP47, TGF-β1, CTGF and TIMP-1 was significantly elevated in HGF gingival fibroblasts compared with controls, while the production of MMP-1 was decreased. CONCLUSIONS We report that fibrosis in HGF gingival tissues is associated with increased synthesis of HSP47. This finding was confirmed by an in vitro study, where excessive production of collagen I was associated with increased synthesis of HSP47, TGF-β1 and CTGF by HGF gingival fibroblasts. Moreover, the shift in the TIMP-1/MMP-1 ratio identifies increased synthesis of TIMP-1 as one of the processes associated with collagen I overproduction in HGF fibroblasts.

Pulp Revascularization after Repositioning of Impacted Incisor with a Dilacerated Root and a Detached Apex

Severely impacted and dilacerated incisors are rarely considered for surgical exposure because they may not respond favorably to orthodontic extrusion. These incisors are often extracted, resulting in the need for tooth replacement; however, prosthetic solutions are limited in growing patients. Transalveolar autotransplantation of an impacted incisor may be the only method to preserve the natural tooth and maintain the shape of the alveolus. The severely impacted upper central incisor (#9) with a developing root was diagnosed in a 9-year-old girl. The unfavorable tooth position and dilaceration of its root made orthodontic extrusion of the impacted incisor impossible. Initial orthodontic space opening at the recipient site was performed before the surgery. Transalveolar transplantation of the impacted incisor to its normal position was performed to avoid tooth extraction. The incisor was later aligned using fixed orthodontic appliances. At the 5-year follow-up, the transplanted incisor presented features that were typical of a revascularized tooth (ie, obliteration of root canal but a positive response to vitality tests). Healthy periodontal tissues and continued root development were also noted. However, the root apex, which separated from the transplant at the time of the surgery, continued formation in its initial position. Transalveolar transplantation of an unfavorably impacted upper central incisor with a dilacerated root is a successful treatment, which stands the test of time. The early stage of root development allowed revascularization of the tooth despite dilaceration of the root and detachment of its apex.

The retrospective study of 93 patients with transmigration of mandibular canine and a comparative analysis with a control group

Summary Objectives The aim of this study was to evaluate characteristics of patients with unilateral transmigration of a mandibular canine in the largest study group presented until now. Materials and methods The study group consisted of 93 patients with unilateral transmigration of mandibular canine; the control group included 85 non-affected patients. Type of transmigration, status of deciduous and permanent canines, prevalence of missing teeth, class of occlusion, and space conditions were assessed to draw comparisons between groups. Results In this study, 64.5 per cent patients presented type 1 of transmigration; types 2, 3, 4, and 5 were present in, respectively, 23.7, 5.4, 4.3, and 2.1 per cent patients. There was a clear, statistically significant difference (P < 0.0001) between the mean crown and apex migration and angulation for the three groups of canines (transmigrated, contralateral, and control), whereas no differences were observed for the total number of permanent teeth present. In the study group, 73.1 per cent patients retained their primary canine on the affected side and 18.3 per cent on the contralateral side; in the control group, 22.3 per cent subjects had at least one primary canine. There was a statistically significant difference in the distribution of types of malocclusion between the study and the control groups. Conclusions Transmigration of mandibular canine was associated with the presence of retained primary canine on the affected side, higher mesial tilting of contralateral mandibular canine when compared to the canines in the control group. Additionally, higher prevalence of Angle’s Class I occlusion in patients with canine transmigration was recorded.

Impacted and transmigrant mandibular canines incidence, aetiology, and treatment: a systematic review

Dear Editor We have read with a great interest the article with the title: “Impacted and transmigrant mandibular canines incidence, aetiology, and treatment: a systematic review” (1) published recently in the EJO, and we would like to congratulate the authors for performing a systematic review on this very interesting topic. However, we feel that the interpretation of the review findings should be re-examined. According to the authors, the reported prevalence of canine impaction in the mandible ranged from 0.92% to 1.35 % and from 0.92% to 5.1 % in the manuscript and the abstract, respectively. After a careful reading, we found that the actual prevalence of the mandibular canine impaction ranged from 0.31% (2) to 1.35% (3). The authors of the review claim that odontomas and lateral incisors anomalies are associated with mandibular canine transmigration. However, the articles included in the review do not support those conclusions. The first study cited in support of this statement included 15 patients where only one patient had an odontoma possibly associated with the transmigrant mandibular canine and two patients with supernumerary teeth (4). In the study by Aydin et al. (5), it is unclear if any of the patients had an odontoma (Table 4) and only one out of eight patients with mandibular canine transmigration presented with missing right maxillary lateral incisors. The study by Gunduz et al. (6) investigated only canine impaction and not canine transmigration. The review findings are also in disagreement with our results from a cohort of 73 patients with transmigration of the mandibular canine where no associations between any oral findings and transmigration were identified (7). In lieu of the above arguments, it seems unjustified to associate odontomas and anomalies of lateral incisors with mandibular canine transmigration. This lack of association is in agreement also with the results of other studies included in the review. In terms of treatment options and prognosis, Mupparapu (8) proposed a classification of transmigrated canines and treatment without considering the type of transmigration (which are clinically very heterogeneous) is not appropriate as not all types of of transmigration are good candidates for orthodontic treatment (for example, severe patterns of transmigration such as the ones occurring in types 2, 3, and 4). The authors reported in the abstract and in Table 4 17% and 17.4% (3) failure of canine eruption after orthodontic traction, whereas according to the article only 16 out of 23 impacted canines erupted successfully indicating a 30% failure. In the other study by Celikoglu et al. (9) four impacted mandibular canines were surgically exposed for orthodontic traction and no further information was provided, however the authors of the review reported 14.28% failure in Table 4. Finally, in the article by Sajnani et al. (2), successful canine eruption after surgical exposure and orthodontic traction was 57.1%. This study was included in the review but information regarding success of orthodontic traction is missing in Table 4. We hope that the authors can clarify these issues and that our comments to this systematic review will improve the understanding of the mandibular canine transmigration phenomenon.

Study on site-specific expression of bone formation and resorption factors in human dental follicles

We sought to investigate site‐specific expression of bone‐regulatory factors expressed by human dental follicles and to compare the stimulated expression of tumour necrosis factor (ligand) superfamily, member 11/tumour necrosis factor receptor superfamily, member 11b (RANKL/OPG) in human dental follicle cells (HDFCs) from different patients. Analysis of bone‐regulatory markers in follicles from 12 different study participants was performed using RT‐qPCR and immunofluorescence; apical and coronal segments from each dental follicle were processed independently. Four additional dental follicles were used for cell cultures; HDFCs were precultured in osteogenic medium to initiate differentiation and thereafter cultured with 10−6 M forskolin (FSK) to activate the protein kinase cAMP (PKA/cAMP) signalling pathway and induce RANKL/OPG expression. We demonstrate that RANKL expression is significantly higher in the coronal part of follicles than in the apical part. High levels of collagen type 1 (COL1), alkaline phosphatase (ALP) and Gap‐junction protein, alpha 1, 43 kDa (CX43) were expressed, whereas expression of Sp7 transcription factor (OSX), bone morphogenetic protein 2 (BMP2), colony‐stimulating factor 1 (CSF‐1), chemokine (C‐C motif) ligand 2 (MCP1), and OPG was low in all samples. The immunofluorescence localization of CSF‐1, MCP1, osteocalcin (OCN), RANKL, and BMP2 was not specific for either part of the follicles. In conclusion, a consistently high expression of CX43 suggests that gap‐junction communication in HDFCs is essential for the eruption process. Furthermore, the induced expression of RANKL in HDFCs varies significantly between individuals and may relate to clinical variations in tooth eruption.

Fibroblasts from recurrent fibrotic overgrowths reveal high rate of proliferation in vitro - findings from the study of hereditary and idiopathic gingival fibromatosis

ABSTRACT Purpose: Investigate the content of fibrotic fibrils in gingival tissue and the proliferation of fibroblasts collected from recurrent and non-recurrent hereditary gingival fibromatosis (HGF) and idiopathic gingival fibromatosis (IGF). Methods: Gingival biopsies were collected from HGF (n = 3) and IGF (n = 3) donors with recurrent and non-recurrent gingival overgrowths and from a control group (Ctrl, n = 3). Hematoxylin staining was performed to evaluate the histomorphology of gingival tissue. Heidenhain’s AZAN trichrome staining served for visualization of fibrotic fibrils in gingiva. Quantitative analysis of the content of fibrotic fibrils in gingival tissue was performed using a polarized light microscope. Proliferation was evaluated at 24 h, 48 h, and 72 h in fibroblast cultures using a cell proliferation ELISA assay based on 5-bromo-2ʹ-deoxyuridine (BrdU). Results: Numerous blood vessels and fibroblasts were observed in recurrent overgrowths, whereas moderate blood vessels and moderate to scanty fibroblasts were detected in non-recurrent overgrowths. Heidenhain’s staining revealed numerous collagen fibers in both recurrent and non-recurrent overgrowths. Quantitative analysis in a polarizing microscope showed significant accumulation of fibrotic fibrils exclusively in the overgrowths with the recurrence. In all time-points, increased proliferation of cells from all recurrent overgrowths was observed, but not from overgrowths which do not reoccur. Conclusions: The study revealed that recurrent gingival overgrowths consist of highly fibrotic and dense connective tissue with numerous blood vessels and abundant fibroblasts. We also demonstrated that unlike fibroblasts derived from overgrowths, which did not present recurrence, fibroblasts derived from highly fibrotic and recurrent overgrowths maintain high rate of proliferation in vitro.

Effect of vestibular deepening on the periodontal status of teeth – preliminary study

Aim of the study. To assess if vestibular deepening improves periodontal parameters of mandibular anterior teeth with gingival recessions. Materials and methods. Ten anterior mandibular teeth in ten patients aged 20 to 49 years with gingival recessions and gingivitis at the mandibular incisors, shallow vestibule and pull-syndrome were examined. Vestibular deepening was performed with modified Kazanjian vestibuloplasty. Probing pocket depth (PPD), clinical attachment level (CAL), gingival recessions (GR), keratinized gingiva (KG), depth of vestibule (VOD), presence of plaque and bleeding were assessed for 98 teeth in total at baseline and at three and twelve months after surgery. Results. Three and twelve months after surgery there was a statistically significant improvement in PPD, CAL and GR when compared to baseline. Mean PPD, CAL and GR were lower (0.3 mm, 1.0 mm and 0.7 mm, respectively) at labial surface of central incisors, and KG significantly increased at labial surface of central and lateral incisors (0.8 mm and 0.6 mm, respectively). The vestibule was deeper at central and lateral incisors, canines and first premolars (3.8 mm, 3.3 mm, 2.3 mm and 0.5 mm, respectively) and the presence of bleeding and plaque was reduced at all assessed teeth. Conclusions. Vestibuloplasty positively changed periodontal parameters at incisors with gingival recessions and did not adversely affect teeth that did not present recessions at the baseline. This type of